The present investigations are designed to evaluate, in a longitudinal and cross-sectional study, the relative contributions of genetic, in utero and nutritional factors to the pathogenesis of childhood obesity. Oral glucose tolerance tests with measurement of serum insulin (or C-peptide) and plasmma glucagon are performed in gestational (Class A) diabetics. Diabetic control is assayed via monthly hemoglobin A1C and total A1, triglyceride, cholesterol and plasma amino acid measurements. Quantitative HDL and LDL, as well as apoproteins are in the initial phase of investigation. Attempts at normalizing maternal blood glucose concentrations in all diabetic pregnant women consist of dietary manipulation, multiple daily insulin injections when required and insulin treatment of gestational diabetic women if their 2-hour post-prandial blood glucose concentrations exceed 140 micrograms/dl or their hemoglobin A1 levels increase significantly. Infants born to these mothers are followed with studies of cord c-peptide and glycosylated hemoglobin. Serial adipose tissue cellularity and metabolic studies and oral glucose tolerance tests are also performed. Serial amino acid, free fatty acid and HDL and LDL measurements are being inaugurated. Growth is monitored with bone age determinations and careful measurements of length, weight, head and abdominal circumference and skinfold thickness. Dietary records are evaluated at monthly clinic visits of the babies and their mothers followed with serial weights and skinfold thickness measurements. Comparison of bottle and breast fed infants are in progress. Preliminary serial studies of red blood cell insulin receptors in the children are in progress for comparison with studies of in vivo insulin sensitivity at various insulin doses. Parallel longitudinal studies are also being performed in obese and normal weight monozygotic and dizygotic twins.